Implementation of DNA methylation array profiling in pediatric central nervous system tumors - the AIM BRAIN Project: an Australian and New Zealand Children&#39;s Haematology and Oncology (ANZCHOG) Group study

White, CL; Kinross, KM; Buntine, MK; Rasouli, E; Strong, R; Jones, JM; Cain, JE; Sturm, D; Sahm, F; Jones, DTW; Pfister, SM; Robertson, T; D&#39;Arcy, C; Rodriguez, ML; Dyke, JM; Junckerstorff, R; Bhuva, DD; Davis, MJ; Wood, P; Hassall, T; Ziegler, DS; Kellie, S; McCowage, G; Alvaro, F; Kirby, M; Heath, JA; Tsui, K; Dodgshun, A; Eisenstat, DD; Khuong-Quang, DA; Wall, M; Algar, EM; Gottardo, NG; Hansford, JR

Implementation of DNA methylation array profiling in pediatric central nervous system tumors - the AIM BRAIN Project: an Australian and New Zealand Children's Haematology and Oncology (ANZCHOG) Group study

Author(s): White, CL; Kinross, KM; Buntine, MK; Rasouli, E; Strong, R; Jones, JM; Cain, JE; Sturm, D; Sahm, F; Jones, DTW; Pfister, SM; Robertson, T; D'Arcy, C; Rodriguez, ML; Dyke, JM; Junckerstorff, R; Bhuva, DD; Davis, MJ; Wood, P; Hassall, T; Ziegler, DS; Kellie, S; McCowage, G; Alvaro, F; Kirby, M; Heath, JA; Tsui, K; Dodgshun, A; Eisenstat, DD; Khuong-Quang, DA; Wall, M; Algar, EM; Gottardo, NG; Hansford, JR;
Details: Publication Year 2023-07-28,Volume 25,Issue #10,Page 709-728
Journal Title: Journal of Molecular Diagnostics
Abstract: DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and inter-laboratory validation studies have been lacking. The AIM BRAIN (AB) diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (DKFZ) (German Cancer Centre Heidelberg, Germany). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥ 0.90 in 176/265 (66.4%) and 213/269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130/176 (74%) (11b4) and 12/174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single work-flow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.
Publisher: Elsevier
Keywords: Child; Humans; Australia; *Central Nervous System Neoplasms/diagnosis/genetics; *DNA Methylation/genetics; New Zealand; Prospective Studies; Reproducibility of Results
Research Division(s): Bioinformatics
PubMed ID: 37517472
Publisher's Version: https://doi.org/10.1016/j.jmoldx.2023.06.013
Open Access at Publisher's Site: https://doi.org/10.1016/j.jmoldx.2023.06.013
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: PIIS1525157823001575.pdf - (2.08MB, application/pdf)

Creation Date: 2023-08-04 12:44:09

Last Modified: 2023-11-20 03:24:10